8-pyridin-3-yl-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinoline-4-thione hydrochloride | 1276123-48-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 8-pyridin-3-yl-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinoline-4-thione hydrochloride
• 英文别名: 8-pyridin-3-yl-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinoline-4-thione hydrochloride
• CAS: 1276123-48-8
• 化学式: C₁₆H₁₄N₂S*ClH
• 分子量: 302.827
• InChiKey: JNHKQMFRYPCLFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.81
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  16.13
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  8-bromo-5,6-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-4(2H)-one 在 劳森试剂 、 盐酸 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 水 、 甲苯 为溶剂， 反应 0.5h， 生成 8-pyridin-3-yl-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinoline-4-thione hydrochloride
  参考文献：
  名称：

  Fine-Tuning the Selectivity of Aldosterone Synthase Inhibitors: Structure−Activity and Structure−Selectivity Insights from Studies of Heteroaryl Substituted 1,2,5,6-Tetrahydropyrrolo[3,2,1-ij]quinolin-4-one Derivatives

  摘要：

  Pyridine substituted 3,4-dihydro-1H-quinolin-2-ones (e.g., 1-3) constitute a class of highly potent and selective inhibitors of aldosterone synthase (CYP11B2), a promising target for the treatment of hyperaldosteronism, congestive heart failure, and myocardial fibrosis. Among these, ethyl-substituted 3 possesses high selectivity against CYP1A2. Rigidification of 3 by incorporation of the ethyl group into a 5- or 6-membered ring affords compounds with a pyrroloquinolinone or pyridoquinolinone molecular scaffold (e.g., 4 and 5). It was found that these molecules are even more potent and selective CYP11B2 inhibitors than their corresponding open-chain analogues. Moreover, pyrroloquinolinone 4 exhibits no inhibition of the six most important hepatic CYP enzymes as well as a bioavailability in the range of the marketed drug fadrozole. The SAR studies disclose that subtle changes in the heterocyclic moiety are responsible for either a strong or a weak inhibition of the highly homologous 11 beta-hydroxylase (CYP11B1). These results are not only important for fine-tuning the selectivity of CYP11B2 inhibitors but also for the development of selective CYP11B1 inhibitors that are of interest for the treatment of Cushing's syndrome and metabolic syndrome.

  DOI：

  10.1021/jm101470k